Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1980 Jul;10(1):67–74. doi: 10.1111/j.1365-2125.1980.tb00503.x

Environmental factors affecting paracetamol metabolism in London factory and office workers.

J C Mucklow, H S Fraser, C J Bulpitt, C Kahn, G Mould, C T Dollery
PMCID: PMC1430020  PMID: 7397056

Abstract

A Paracetamol elimination was measured, using serial saliva samples, in 114 London factory and office workers, 76 Whites and 38 Asian immigrants. 2. Use of social drugs such as alcohol, tobacco and the oral contraceptive varied considerably within the sample, being appreciably greater in White subjects. 3. Paracetamol clearance was 21% slower in Asians than in Whites and half-life 18% longer. The total range of clearance was 1.86--6.78 ml min-1 kg-1. 4. Clearance was slower in women than in men, increased with increasing alcohol intake and cigarett consumption, and was more rapid in those women using the oral contraceptive. The effects of alcohol and the oral contraceptive were also found in White subjects alone. 5 The variables found to correlate independently with paracetamol clearance accounted for only 27% of the total sample variance, however, and are unlikely to be the major determinants of paracetamol elimination in man.

Full text

PDF
67

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexanderson B., Evans D. A., Sjöqvist F. Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. Br Med J. 1969 Dec 27;4(5686):764–768. doi: 10.1136/bmj.4.5686.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alvares A. P. Research review. Interactions between environmental chemicals and drug biotransformation in man. Clin Pharmacokinet. 1978 Nov-Dec;3(6):462–477. doi: 10.2165/00003088-197803060-00004. [DOI] [PubMed] [Google Scholar]
  3. Bolanowska W., Gessner T. Drug interactions: inhibition of acetaminophen glucuronidation by drugs. J Pharmacol Exp Ther. 1978 Jul;206(1):233–238. [PubMed] [Google Scholar]
  4. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  5. Cummings A. J., King M. L., Martin B. K. A kinetic study of drug elimination: the excretion of paracetamol and its metabolites in man. Br J Pharmacol Chemother. 1967 Feb;29(2):150–157. doi: 10.1111/j.1476-5381.1967.tb01948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fraser H. S., Mucklow J. C., Bulpitt C. J., Kahn C., Mould G., Dollery C. T. Environmental factors affecting antipyrine metabolism in London factory and office workers. Br J Clin Pharmacol. 1979 Mar;7(3):237–243. doi: 10.1111/j.1365-2125.1979.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fraser H. S., Mucklow J. C., Murray S., Davies D. S. Assessment of antipyrine kinetics by measurement in saliva. Br J Clin Pharmacol. 1976 Apr;3(2):321–325. doi: 10.1111/j.1365-2125.1976.tb00610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fulton B., James O., Rawlins M. D. The influence of age on the pharmacokinetics of paracetamol [proceedings]. Br J Clin Pharmacol. 1979 Apr;7(4):418P–418P. [PubMed] [Google Scholar]
  9. Glynn J. P., Bastain W. Salivary excretion of paracetamol in man. J Pharm Pharmacol. 1973 May;25(5):420–421. doi: 10.1111/j.2042-7158.1973.tb10042.x. [DOI] [PubMed] [Google Scholar]
  10. Hamada N., Gessner T. Effect of 3-methylcholanthrene pretreatment on glucuronidation and sulfation in perfused rat liver. Drug Metab Dispos. 1975 Sep-Oct;3(5):407–416. [PubMed] [Google Scholar]
  11. Hammer W., Sjöqvist F. Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci. 1967 Sep 1;6(17):1895–1903. doi: 10.1016/0024-3205(67)90218-4. [DOI] [PubMed] [Google Scholar]
  12. LOESER E. W., Jr Studies on the metabolism of diphenylhydantoin (Dilantin). Neurology. 1961 May;11:424–429. doi: 10.1212/wnl.11.5.424. [DOI] [PubMed] [Google Scholar]
  13. Perucca E., Richens A. Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol. 1979 Feb;7(2):201–206. doi: 10.1111/j.1365-2125.1979.tb00922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Prescott L. F. Gas-liquid chromatographic estimation of paracetamol. J Pharm Pharmacol. 1971 Oct;23(10):807–808. doi: 10.1111/j.2042-7158.1971.tb08613.x. [DOI] [PubMed] [Google Scholar]
  15. Rawlins M. D., Henderson D. B., Hijab A. R. Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration. Eur J Clin Pharmacol. 1977 Apr 20;11(4):283–286. doi: 10.1007/BF00607678. [DOI] [PubMed] [Google Scholar]
  16. Shively C. A., Vesell E. S. Temporal variations in acetaminophen and phenacetin half-life in man. Clin Pharmacol Ther. 1975 Oct;18(4):413–424. doi: 10.1002/cpt1975184413. [DOI] [PubMed] [Google Scholar]
  17. Thomas B. H., Zeitz W., Beaubien A. R. Effect of subacute dosing and phenobarbital and 3-methylcholanthrene pretreatment on the metabolism of acetaminophen in rats. Can J Physiol Pharmacol. 1977 Feb;55(1):77–83. doi: 10.1139/y77-011. [DOI] [PubMed] [Google Scholar]
  18. Uotila P., Marniemi J. Variable effects of cigarette smoking on aryl hydrocarbon hydroxylase, epodixe hydratase and UDP-glucuronosyltransferase activities in rat lung, kidney and small intestinal mucosa. Biochem Pharmacol. 1976 Oct 15;25(20):2323–2328. doi: 10.1016/0006-2952(76)90017-4. [DOI] [PubMed] [Google Scholar]
  19. Vesell E. S. Genetic and environmental factors affecting drug response in man. Fed Proc. 1972 Jul-Aug;31(4):1253–1269. [PubMed] [Google Scholar]
  20. Vesell E. S., Page J. G., Passananti G. T. Genetic and environmental factors affecting ethanol metabolism in man. Clin Pharmacol Ther. 1971 Mar-Apr;12(2):192–201. doi: 10.1002/cpt1971122part1192. [DOI] [PubMed] [Google Scholar]
  21. Winsnes A. Age and sex dependent variability of the activation characteristics of UDP-glucuronyltransferase in vitro. Biochem Pharmacol. 1971 Jun;20(6):1249–1258. doi: 10.1016/0006-2952(71)90355-8. [DOI] [PubMed] [Google Scholar]
  22. Wishart G. J. Demonstration of functional heterogeneity of hepatic uridine diphosphate glucuronosyltransferase activities after administration of 3-methylcholanthrene and phenobarbital to rats. Biochem J. 1978 Aug 15;174(2):671–672. doi: 10.1042/bj1740671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wishart G. J. Functional heterogeneity of UDP-glucuronosyltransferase as indicated by its differential development and inducibility by glucocorticoids. Demonstration of two groups within the enzyme's activity towards twelve substrates. Biochem J. 1978 Aug 15;174(2):485–489. doi: 10.1042/bj1740485. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES